Objective:The identification of biomarkers for predicting chemoradiotherapy efficacy is essential to optimize personalized treatment.This study determined the effects of genetic variations in genes involved in apoptos...Objective:The identification of biomarkers for predicting chemoradiotherapy efficacy is essential to optimize personalized treatment.This study determined the effects of genetic variations in genes involved in apoptosis,pyroptosis,and ferroptosis on the prognosis of patients with locally advanced rectal cancer receiving postoperative chemoradiotherapy(CRT).Methods:The Sequenom MassARRAY was used to detect 217 genetic variations in 40 genes from 300 patients with rectal cancer who received postoperative CRT.The associations between genetic variations and overall survival(OS)were evaluated using hazard ratios(HRs)and 95%confidence intervals(CIs)computed using a Cox proportional regression model.Functional experiments were performed to determine the functions of the arachidonate 5-lipoxygenase(ALOX5)gene and the ALOX5 rs702365 variant.Results:We detected 16 genetic polymorphisms in CASP3,CASP7,TRAILR2,GSDME,CASP4,HO-1,ALOX5,GPX4,and NRF2 that were significantly associated with OS in the additive model(P<0.05).There was a substantial cumulative effect of three genetic polymorphisms(CASP4 rs571407,ALOX5 rs2242332,and HO-1 rs17883419)on OS.Genetic variations in the CASP4 and ALOX5 gene haplotypes were associated with a higher OS.We demonstrated,for the first time,that rs702365[G]>[C]represses ALOX5 transcription and corollary experiments suggested that ALOX5 may promote colon cancer cell growth by mediating an inflammatory response.Conclusions:Polymorphisms in genes regulating cell death may play essential roles in the prognosis of patients with rectal cancer who are treated with postoperative CRT and may serve as potential genetic biomarkers for individualized treatment.展开更多
Objective To investigate acid-suppression efficacy of proton pump inhibitors(PPIs) in relation to CYP2C19 genetic polymorphism on patients with peptic ulcer. Methods By an open, randomized and control trial, fifty nin...Objective To investigate acid-suppression efficacy of proton pump inhibitors(PPIs) in relation to CYP2C19 genetic polymorphism on patients with peptic ulcer. Methods By an open, randomized and control trial, fifty nine patients with active peptic ulcer were randomly assigned to receive one of three PPIs on a single dose (20 mg of each drug): omeprazole group (n=19), rabeprazole group (n=20) and esomeprazole group (n=20). Intragastric pH was recorded 1 hour before and 24 hours after administration. CYP2C19 genotype was tested in all patients. Results The EMs/PMs ratio of each group was 16/3,17/3 and 17/3, respectively. The total time that intragastric pH>4, time percent pH>4 and median pH in PMs patients were significantly higher than those in EMs patients of omeprazole group (P<0.05). But all these differences were not found in rabeprazole group and esomeprazole group. The pH of nocturnal acid breakthrough(NAB) in both rabeprazole group and esomeprazole group was higher than that of omeprazole group, while there was no significant difference between rabeprazole group and esomeprazole group.Conclusion The acid-suppression efficacy of omeprazole is highly dependent on CYP2C19 genetic polymorphism, while CYP2C19 genetic polymorphism may have a little influence on the acid-suppression efficacy of rabeprazole and esomeprazole. The acid-suppression action of rabeprazole and esomeprazole is superior to omeprazole, especially on night acid secretion.展开更多
Objective To analyze the genetic polymorphism of 6 STR loci (D12S358, D12S1675, D12S1663, D12S1697, D12S1725 and D12S1613) on chromosome 12 in Chinese Han population. Methods EDTA-blood specimens were collected from 1...Objective To analyze the genetic polymorphism of 6 STR loci (D12S358, D12S1675, D12S1663, D12S1697, D12S1725 and D12S1613) on chromosome 12 in Chinese Han population. Methods EDTA-blood specimens were collected from 153 unrelated individuals of Chinese Han population in Shaanxi province. Allele and genotype frequencies for the 6 STR loci were estimated and statistical parameters of polymorphism were calculated. Results 8 alleles and 18 genotypes, 10 alleles and 17 genotypes, 9 alleles and 15 genotypes, 12alleles and 29 genotypes, 12 alleles and 31 genotypes, 8 alleles and 11 genotypes were observed at D12S358, D12S1675, D12S1663, D12S1697, D12S1725 and D12S1613, respectively. No deviations of the observed allele frequency from Hardy-weinberg equilibrium expectations were found for any of these loci. The Heterozygotes of these 6 loci were 78.89%, 66.10%, 54.95%, 79.10%, 71.98% and 59.48%, respectively. It indicated the high genetic polymorphism of the loci in Chinese Han population. Conclusion The 6 STR loci belonged to the genetic marker system of high discriminutesation and high information in Chinese Han population and can be used in the study of gene-related diseases.展开更多
Objective To reveal the relationship between the 5-HTTLPR and the Chinese Han nationality children with CA, compared the distribution of the 5-HTTLPR between the Han Chinese children with CA and healthy Han Chinese ch...Objective To reveal the relationship between the 5-HTTLPR and the Chinese Han nationality children with CA, compared the distribution of the 5-HTTLPR between the Han Chinese children with CA and healthy Han Chinese children ,and analyzed the association between the 5-HTTLPR and clinical symptoms of the Han Chinese children with CA. Methods Genomic DNAs of fifty subjects including 25 autistic children and 25 controls were extracted from blood samples. PCR amplification using Oligonucleotide primers flanking 5-HTTLPR was performed. Results ① Three kinds of alleles including the S (short) allele, the L (long) allele and the VL allele were found , and the 5-HTTLPR genotypes shown were S/S, L/L, S/L and L/VL. ② Allele frequencies did not differ significantly in patient groups in comparison with the control sample. No significant difference was identified between the observed 5-HTTLPR genotype distribution of the patient groups and control group. ③ The distribution of homozygous and heterozygous subjects between the two groups differed significantly. ④ The genotypes of the 5-HTTLPR polymorphism correlated significantly with the Body Movement Factor. ⑤ The allele frequency of healthy Han Chinese population and that of healthy Japanese population were similar. The frequency of S allele in not only autistic subjects but also healthy children in this study was considerably more than that in Caucasians and the frequency of L allele in our subjects decreased correspondingly. Conclusion ① A significant difference in the allele frequency between the Han Chinese and Caucasian populations was found. ② The genotypes of the 5-HTTLPR polymorphism correlated significantly with the Body Movement Factor of the patients. ③ The homozygote and the L allele were positively relevant to CA and they might be the risk factors of CA. The heterozygote and the S allele were negatively relevant to CA and they might be the protective factors of CA.展开更多
While we studied pharmacokinetics of SM-12502 which was under development as an anti-PAF agent, we found three subjects showing a slow metabolic phenotype in its pharmacokinetics. Analyzing the genes for CYP2A6 from t...While we studied pharmacokinetics of SM-12502 which was under development as an anti-PAF agent, we found three subjects showing a slow metabolic phenotype in its pharmacokinetics. Analyzing the genes for CYP2A6 from the three subjects, we discovered that the three subjects possessed the whole CYP2A6 gene deletion (CYP2A6*4C), a novel genetic polymorphism of the CYP2A6 gene. Genetically engineered Salmonella YG7108 cells expressing human CYP2A6 or CYP2E1 together with the NADPH-CYP reductase were established in our laboratory to compare the mutagen-producing capacity of these enzymes for various N-nitrosamines. We found that CYP2E1 was responsible for the metabolic activation of N-nitrosamines with relatively short alkyl chains, whereas CYP2A6 was involved in the metabolic activation of N-nitrosamines possessing relatively bulky alkyl chains such as a tobacco-specific nitrosamine, NNK, which has been known to cause lung tumor in rodents. Thus, to examine a hypothesis that individuals possessing the CYP2A6*4C have the reduced risk of lung cancer due to the lack of the capacity of the metabolic activation of certain carcinogens in tobacco smoke, a case-control study was performed.展开更多
Objective To analyze the relationship between genetic polymorphisms of organic anion transporting polypeptide ( SLCO1B1 and SLCO1B3) and mycophenolic acid ( MPA) pharmacokinetics in Chinese kidney transplant recipient...Objective To analyze the relationship between genetic polymorphisms of organic anion transporting polypeptide ( SLCO1B1 and SLCO1B3) and mycophenolic acid ( MPA) pharmacokinetics in Chinese kidney transplant recipients. Methods Gene mutations ( SLCO1B3 T334G,SLCO1B1 A338G) were detected in 68 recipi-展开更多
AIM: Genetic polymorphism in enzymes of carcinogen metabolism has been found to have the influence on the susceptibility to cancer. Cytochrome P450 2E1 ( CYP2 E1) is considered to play an important role in the metabol...AIM: Genetic polymorphism in enzymes of carcinogen metabolism has been found to have the influence on the susceptibility to cancer. Cytochrome P450 2E1 ( CYP2 E1) is considered to play an important role in the metabolic activation of procarcinogens such as N-nitroscoamines and Iow molecular weight organic compounds. The purpose of this study is to determine whether CYP450 2Elpolymorphisms are associated with risk s of gastric cancer.METHODS: We conducted a population based case-control study in Changle county, Fujian Province, a high-risk region of gastric cancer in China. Ninety-one incident gastric cancer patients and ninety-four healthy controls were included in our study. Datas including dsmographic characteristcs, diet intake, and alcohol and tobacco consumption of indivduals in our study were completed by a standardized questionnaire. PCR-RFLP revealed three genotypes: heterozygote (C1/C2) and two homozygotes (C1/C1 and C2/C2) in CYP2E1.RESULTS: The frequency of variant genotypes (C1/C2 and C2/C2) in gastric cancer cases and controls was 36.3% and 24.5%, respectively. The rare homozygous C2/C2 genotype was found in 6 indivduals in gastric cancer group(6.6%),whereas there was only one in the control group (1.1%).However, there was no statistically significan difference between the two groups (two-tailed Fisher′s exact test, P =0.066). Indivduals in gastric cancer group were more likely to carry genotype C1/C2 (odds ratio, OR = 1.50) and C2/C2(OR = 7.34) than indivduals in control group (X2 = 4.597, for trend P=0.032). The frequencies of genofypes with the C2allele ( C1/C2 and C2/C2 genotypes) were compared with those of genotypes without C2 allele ( C1/C1 genotype )among indivduals in gastric cancer group and control group according to the pattern of gastric cancer risk factors. The results show that indivduals who exposed to these gastric cancer risk factors and carry the C2 allele seemed to have a higher risk of developing gastric cancer.CONCLUSION: Polymorphism of CYP2E1 gene may have some effct in the development of gastric cancer in Changle county, Fujian Province.展开更多
BACKGROUND:Alcohol abuse and dependence are major factors in the pathogenesis of alcoholic liver disease(ALD).Alcohol abuse is becoming an increasingly severe problem among the Han,Mongol,and Korean nationalities in n...BACKGROUND:Alcohol abuse and dependence are major factors in the pathogenesis of alcoholic liver disease(ALD).Alcohol abuse is becoming an increasingly severe problem among the Han,Mongol,and Korean nationalities in northeast China.This study aimed to investigate the relationship between ALD and the genetic polymorphism and expression levels of two enzymes,cytochrome P450ⅡE1(CYPⅡE1)and glutathione S-transferase P1(GSTP1)in patients of three nationalities.METHODS:Peripheral blood was collected from 353 Chinese patients with ALD,300 alcohol dependent patients without liver disease(alcoholic),and 360 healthy controls.Each group included patients from the Han,Mongol and Korean nationalities.Real-time polymerase chain reaction(PCR)and PCR-restriction fragment length polymorphism(PCR-RFLP)were used.RESULTS:Regardless of nationality,patients who carried the rare CYPⅡE1 C2 and GSTP1 Val alleles were at higher risk of ALD.The frequency of C2 and Val in patients with ALD was respectively 50.00% and 26.98% in the Han,31.36% and 22.87% in the Mongol,and 45.87% and 22.02% in the Korean nationality.No significant differences were seen in the frequency of either C2 or Val alleles in ALD patients among the three nationalities.In each nationality,the frequency of both C2 and Val alleles was significantly higher in ALD compared to alcoholic and healthy controls.Except for nationality,the average mRNA levels of CYPⅡ E1 in ALD patients and healthy controls were 10.05%and 2.21%,respectively.The average mRNA levels of GSTP1 in ALD patients and healthy controls were 0.53%and 2.12%,respectively.The mRNA level of CYPⅡE1 was higher,and that of GSTP1 was lower in patients with ALD compared to the controls.CONCLUSIONS:Except for nationality,patients with ALD in this series tended to have a higher mRNA expression of CYPⅡE1 and to carry the C2 allele,and tended to have a lower mRNA expression of GSTP1 and to carry the Val allele.There is a causal relationship between the polymorphic alleles,which leads to different mRNA levels and the development of ALD.展开更多
Irritable bowel syndrome(IBS)is a complex symptombased disorder without established biomarkers or putative pathophysiology.IBS is a common functional gastrointestinal disorder which is defined as recurrent abdominal p...Irritable bowel syndrome(IBS)is a complex symptombased disorder without established biomarkers or putative pathophysiology.IBS is a common functional gastrointestinal disorder which is defined as recurrent abdominal pain or discomfort that has at least two of the following symptoms for 3 d per month in the past 3mo according to ROMEⅢ:relief by defecation,onset associated with a change in stool frequency or onset with change in appearance or form of stool.Recent discoveries revealed genetic polymorphisms in specific cytokines and neuropeptides may possibly influence the frequencies and severity of symptoms,as well as the therapeutic responses in treating IBS patients.This review gives new insights on how genetic determinations influence in clinical manifestations,treatment responses and potential biomarkers of IBS.展开更多
AIM: To correlate a genetic polymorphism of the low-density lipoprotein(LDL) receptor with antiviral responses in Egyptian chronic hepatitis C virus(HCV) patients.METHODS: Our study included 657 HCV-infected patients ...AIM: To correlate a genetic polymorphism of the low-density lipoprotein(LDL) receptor with antiviral responses in Egyptian chronic hepatitis C virus(HCV) patients.METHODS: Our study included 657 HCV-infected patients with genotype 4 who received interferonbased combination therapy. Patients were divided into two groups based on their response to therapy: 356 were responders, and 301 were non-responders. Patients were compared to 160 healthy controls. All patients and controls underwent a thorough physical examination, measurement of body mass index(BMI) and the following laboratory tests: serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, albumin, total bilirubin, direct bilirubin, prothrombin time, prothrombin concentration, INR, complete blood count, serum creatinine, fasting blood sugar, HCV antibody, and hepatitis B surface antigen. All HCV patients were further subjected to the following laboratory tests: HCV-RNA using quantitative polymerase chain reaction(PCR), antinuclear antibodies, thyroid-stimulating hormone, an LDL receptor(LDLR) genotype study of LDLR exon8 c.1171G>A and exon-10 c.1413G>A using real-time PCR-based assays, abdominal ultrasonography, ultrasonographic-guided liver biopsy, and histopathological examination of liver biopsies. Correlations of LDL receptor polymorphisms with HAI, METAVIR score, presence of steatosis, and BMI were performed in all cases.RESULTS: There were no statistically significant differences in response rates between the different types of interferon used or LDLR exon10 c.1413G>A. However, there was a significant difference in the frequency of the LDL receptor exon8 c.1171G>A genotype between cases(AA: 25.9%, GA: 22.2%, GG: 51.9%) and controls(AA: 3.8%, GA: 53.1% and GG: 43.1%)(P < 0.001). There was a statistically significant difference in the frequency of the LDLR exon 8C:1171 G>A polymorphism between responders(AA: 3.6%, GA: 15.2%, GG: 81.2%) and nonresponders(AA: 52.2%, GA: 30.6%, GG: 17.2%)(P < 0.001). The G allele of LDL receptor exon8 c.1171G>A predominated in cases and controls over the A allele, and a statistically significant association with response to interferon was observed. The frequency of the LDLR exon8 c.1171G>A allele in non-responders was: A: 67.4% and G: 32.6 vs A: 11.2% and G: 88.8% in responders(P < 0.001). Therefore, carriers of the A allele exhibited a 16.4 times greater risk for nonresponse. There was a significant association between LDL receptors exon8 c.1171G>A and HAI(P < 0.011). There was a significant association between LDL receptors exon8 c.1171G>A and BMI. The mean BMI level was highest in patients carrying the AA genotype(28.7 ± 4.7 kg/m2) followed by the GA genotype(28.1 ± 4.8 kg/m2). The lowest BMI was the GG genotype(26.6 ± 4.3 kg/m2)(P < 0.001). The only significant associations were found between LDL receptors exon8 c.1171G>A and METAVIR score or steatosis(P < 0.001).CONCLUSION: LDL receptor gene polymorphisms play a role in the treatment response of HCV and the modulation of disease progression in Egyptiansinfected with chronic HCV.展开更多
Genetic polymorphism is associated with irritable bowel syndrome(IBS)in terms of susceptibility and clinical manifestations.Previous studies have shown that genetic polymorphism might play a key role in the onset and ...Genetic polymorphism is associated with irritable bowel syndrome(IBS)in terms of susceptibility and clinical manifestations.Previous studies have shown that genetic polymorphism might play a key role in the onset and progression of IBS by modulating components of its pathogenesis such as the gut-brain axis,gastrointestinal motility,inflammatory activity,and immune status.Although underlying pathophysiological mechanisms have not been fully clarified,the potential ethnic differences that are present in worldwide genetic studies of IBS deserve attention.This review surveyed numerous studies focusing on IBSassociated single nucleotide polymorphisms,and investigated the ethnic disparities revealed by them.The results demonstrate the need for more attention on ethnic factors in IBS-related genetic studies.Taking ethnic backgrounds into accounts and placing emphasis on disparities potentially ascribed to ethnicity could help lay a solid and generalized foundation for transcultural,multi-ethnic,or secondary analyses in IBS,for example,a meta-analysis.Broader genetic studies considering ethnic factors are greatly needed to obtain a better understanding of the pathophysiological mechanisms of IBS and to improve the prevention,intervention,and treatment of this disease.展开更多
AIM:To investigate the correlation between interleukin-18(IL-18) gene polymorphisms and the risk of developing Crohn's disease(CD).METHODS:The PubMed,CISCOM,CINAHL,Web of Science,EBSCO,Cochrane Library,MEDLINE,EMB...AIM:To investigate the correlation between interleukin-18(IL-18) gene polymorphisms and the risk of developing Crohn's disease(CD).METHODS:The PubMed,CISCOM,CINAHL,Web of Science,EBSCO,Cochrane Library,MEDLINE,EMBASE and CBM databases were searched without any language restrictions using combinations of keywords relating to CD and IL-18 for relevant articles published before November 1st,2013.Screening of the published studies retrieved from searches was based on our stringent inclusion and exclusion criteria and resulted in seven eligible studies for meta-analysis.A metaanalysis was conducted using a random-effects model with STATA 12.0 software.Crude odds ratios(ORs) with95%confidence intervals(95%CI) were calculated.RESULTS:Seven case-control studies,with a total of1930 CD cases and 1930 healthy subjects,met our inclusion criteria.The results of our meta-analysis indicated that the IL-18 rs1946518 A>C and rs187238G>C polymorphisms may correlate with an increased risk of CD under five genetic models(all P < 0.05).Furthermore,we observed positive associations between the IL-18 rs360718 A>C polymorphism and CD risk under three genetic models(C allele vs A allele:OR = 2.03,95%CI:1.20-3.43,P = 0.008;CC vs AA+AC:OR = 2.39,95%CI:1.2-4.43,P = 0.006;CC vs AC:OR = 2.31,95%CI:1.22-4.38,P = 0.010).However,such associations were not found for the IL-18 rs917997 C>T,codon 35 A>C and rs1946519G>T polymorphisms(all P> 0.05).A subgroup analysis was conducted to investigate the effect of ethnicity on an individual's susceptibility to CD.Our results revealed positive correlations between IL-18 genetic polymorphisms and an increased risk of CD among Asians and Africans(all P < 0.05),but not among Caucasians(all P> 0.05).CONCLUSION:This meta-analysis indicated that the IL-18 rs1946518 A> C,rs187238 G>C and rs360718A>C polymorphisms may contribute to susceptibility to CD,especially among Asians and Africans.These polymorphisms are known to reduce IL-18 mRNA and protein levels.展开更多
interleukin(iL)28B genetic polymorphism is significantly associated with the sustained virological response rate in patients with chronic hepatitis C treated with pegylated interferon-α(PEG-iFN)plus ribavirin and wit...interleukin(iL)28B genetic polymorphism is significantly associated with the sustained virological response rate in patients with chronic hepatitis C treated with pegylated interferon-α(PEG-iFN)plus ribavirin and with spontaneous hepatitis C virus clearance.However,a consensus on the relationship between iL28B genetic polymorphism and the favorable outcome of chronic hepatitis B virus infection defined by hepatitis B e antigen seroconversion,and/or hepatitis B surface antigen seroclearance in patients treated with interferon or PEG-iFN has not been reached.Several reports failed to show a positive association,while some studies demonstrated a positive association in certain subject settings.More prospective studies including large cohorts are needed to determine the possible association between iL28B genetic polymorphism and the outcome of interferon or PEG-iFN treatment for chronic hepatitis B.展开更多
Objective:To investigate the genetic polymorphism of Plasmodium vivax(P.vivax) PvCSP and PvMSP1 genes from field isolates at four endemic regions(North,East,West and South) of Thailand.Methods:The 152 P.vivax injected...Objective:To investigate the genetic polymorphism of Plasmodium vivax(P.vivax) PvCSP and PvMSP1 genes from field isolates at four endemic regions(North,East,West and South) of Thailand.Methods:The 152 P.vivax injected cases from dried blood spots were DMA extracted and confirmed by species-specific primer sets using multiplex PCR method.PvMSPI fragments F2 and F3:PvCSP were gcnotvped using RFLP-PCR method.Resuits:Totally amplified DNA which was multiple genotypes for PvMSP1 F2 and PvMSP1 F3 were 12.50%and 8.55%.respectively while PvCSP was 3.95%.The overall frequency of multiple genotypes was 25%.There were 12 allele tvpes of PvMSP1 F2 using AluI enzyme digestion and 8 size variations were found in P\MSP1 F3.The isolates from western region was highly genetic diverse when compare among all isolates.The predominant variant type of PvCSP gene was \ K2I0 type.Conclusions:The niulliple genotypes are common found in Thailand and it might hide the real genotype.PvCSP does not have extensive genetic diversity in this study.However.PvMSPI marker due to multiple genotypes is difficult In be analyzed.The multiple genotypes findings might stem from population migration and vector species findings.展开更多
BACKGROUND:Recurrence of hepatocellular carcinoma(HCC) after liver transplantation(LT) remains one of the most common causes of poor long-term survival.However,the host genetic factors affecting increased risk of tumo...BACKGROUND:Recurrence of hepatocellular carcinoma(HCC) after liver transplantation(LT) remains one of the most common causes of poor long-term survival.However,the host genetic factors affecting increased risk of tumor recurrence after transplantation have not been thoroughly elucidated.The present study was designed to investigate the association of cytokine gene polymorphisms with the risk of tumor recurrence in LT patients for HCC.METHODS:Eleven single-nucleotide polymorphisms within the promoter regions of 7 cytokine genes,i.e.,the IL-1 family(IL-1α and IL-1β),IL-6,IL-8,IL-10,TNF-α,and TGF-β1,were genotyped in 93 HCC patients treated with LT using DNA sequencing.The association between these polymorphisms and the risk of tumor recurrence was evaluated while controlling confounding clinical variables.RESULTS:The genotype frequency of IL-10-1082 A/G in patients with and without recurrence of HCC was AA 83.3%,GA 16.7% and AA 97.6%,GA 2.4%,respectively.The association between IL-10-1082 GA and recurrence was significant(P=0.033).No other single-nucleotide polymorphism in the cytokine gene was found to be associated with recurrence.Kaplan-Meier survival curves showed that the homozygous AA patients had a significantly longer mean recurrence-free survival than heterozygous GA patients(23.5 vs 5.7 months,P=0.001).However,multivariate analysis failed to reveal that the GA genotype of IL-10-1082 A/G was an independent indicator of recurrence.CONCLUSIONS:This study suggests the lack of association of selected cytokine gene polymorphisms with HCC recurrence after LT in the Han Chinese population.The finding does not exclude the idea that other cytokine polymorphisms could act as candidate biomarkers of disease prognosis.展开更多
Diabetes mellitus is a combined metabolic disorder which includes hyperglycemia,dyslipidemia,stroke and several other complications.Various groups all over the world are relentlessly working out the possible role of a...Diabetes mellitus is a combined metabolic disorder which includes hyperglycemia,dyslipidemia,stroke and several other complications.Various groups all over the world are relentlessly working out the possible role of a vast number of genes associated with type 2 diabetes(T2DM).Inflammation is an important outcome of any kind of imbalance in the body and is therefore an indicator of several diseases,including T2DM.Various ethnic populations around the world show different levels of variations in single nucleotide polymorphisms(SNPs).The present review was undertaken to explore the association of cytokine gene polymorphisms with T2DM in populations of different ethnicities.This will lead to the understanding of the role of cytokine genes in T2DM risk and development.Association studies of genotypes of SNPs present in cytokine genes will help to identify risk haplotype(s)for disease susceptibility by developing prognostic markers and alter treatment strategies for T2DM and related complications.This will enable individuals at risk to take prior precautionary measures and avoid or delay the onset of the disease.Future challenges will be to understand the genotypic interactions between SNPs in one cytokine gene or several genes at different loci and study their association with T2DM.展开更多
Objective: In the past few decades, more than 500 reports have been published on the relationship between single nucleotide polymorphisms(SNPs) on candidate genes and gastric cancer(GC) risk. Previous findings have be...Objective: In the past few decades, more than 500 reports have been published on the relationship between single nucleotide polymorphisms(SNPs) on candidate genes and gastric cancer(GC) risk. Previous findings have been disputed and are controversial. Therefore, we performed this article to summarize and assess the credibility and strength of genetic polymorphisms on the risk of GC.Methods: We used Web of Science, PubMed, and Medline to identify meta-analyses published before July 30 th, 2018 that assessed associations between variants on candidate genes and the risk of GC. Cumulative epidemiological evidence of statistical associations was assessed combining Venice criteria and a false-positive report probability(FPRP) test.Results: Sixty-one variants demonstrated a significant association with GC risk, whereas 29 demonstrated no association. Nine variants on nine genes were rated as presenting strong cumulative epidemiological evidence for a nominally significant association with GC risk, including APE1(rs1760944), DNMT1(rs16999593), ERCC5(rs751402), GSTT1(null/presence), MDM2(rs2278744), PPARG(rs1801282), TLR4(rs4986790), IL-17 F(rs763780), and CASP8(rs3834129). Eleven SNPs were rated as moderate, and 33 SNPs were rated as weak. We also used the FPRP test to identify 13 noteworthy SNPs in five genome-wide association studies.Conclusions: Sixty-one variants are significantly associated with GC risk, and 29 variants are not associated with GC risk;however, five variants on five genes presented strong evidence for an association upgraded from moderate. Further study of these variants may be needed in the future. Our study also provides referenced information for the genetic predisposition to GC.展开更多
Two common polymorphisms of the peroxisome proliferator-activated receptor gamma(PPARG) gene, rs1801282 and rs3856806, may be important candidate gene loci affecting the susceptibility to ischemic stroke. This case-co...Two common polymorphisms of the peroxisome proliferator-activated receptor gamma(PPARG) gene, rs1801282 and rs3856806, may be important candidate gene loci affecting the susceptibility to ischemic stroke. This case-control study sought to identify the relationship between these two single-nucleotide polymorphisms and ischemic stroke risk in a northern Chinese Han population. A total of 910 ischemic stroke participants were recruited from the First Hospital of China Medical University, Shenyang, China as a case group, of whom 895 completed the study. The 883 healthy controls were recruited from the Health Check Center of the First Hospital of China Medical University, Shenyang, China. All participants or family members provided informed consent. The study protocol was approved by the Ethics Committee of the First Hospital of China Medical University, China on February 20, 2012(approval No. 2012-38-1). The protocol was registered with the Chinese Clinical Trial Registry(registration number: ChiCTR-COC-17013559). Plasma genomic DNA was extracted from all participants and analyzed for rs1801282 and rs3856806 single nucleotide polymorphisms using a SNaPshot Multiplex sequencing assay. Odds ratios(ORs) and 95% confidence intervals(CIs) were calculated using unconditional logistic regression to estimate the association between ischemic stroke and a particular genotype. Results demonstrated that the G allele frequency of the PPARG gene rs1801282 locus was significantly higher in the case group than in the control group(P < 0.001). Individuals carrying the G allele had a 1.844 fold increased risk of ischemic stroke(OR = 1.844, 95% CI: 1.286–2.645, P < 0.001). Individuals carrying the rs3856806 T allele had a 1.366 fold increased risk of ischemic stroke(OR = 1.366, 95% CI: 1.077–1.733, P = 0.010). The distribution frequencies of the PPARG gene haplotypes rs1801282-rs3856806 in the control and case groups were determined. The frequency of distribution in the G-T haplotype case group was significantly higher than that in the control group. The risk of ischemic stroke increased to 2.953 times in individuals carrying the G-T haplotype(OR = 2.953, 95% CI: 2.082–4.190, P < 0.001). The rs1801282 G allele and rs3856806 T allele had a multiplicative interaction(OR = 3.404, 95% CI: 1.631–7.102, P < 0.001) and additive interaction(RERI = 41.705, 95% CI: 14.586–68.824, AP = 0.860;95% CI: 0.779–0.940;S = 8.170, 95% CI: 3.772–17.697) on ischemic stroke risk, showing a synergistic effect. Of all ischemic stroke cases, 86% were attributed to the interaction of the G allele of rs1801282 and the T allele of rs3856806. The effect of the PPARG rs1801282 G allele on ischemic stroke risk was enhanced in the presence of the rs3856806 T allele(OR = 8.001 vs. 1.844). The effect of the rs3856806 T allele on ischemic stroke risk was also enhanced in the presence of the rs1801282 G allele(OR = 2.546 vs. 1.366). Our results confirmed that the G allele of the PPARG gene rs1801282 locus and the T allele of the rs3856806 locus may be independent risk factors for ischemic stroke in the Han population of northern China, with a synergistic effect between the two alleles.展开更多
AIM: To investigate the association between interleukin-10(IL-10) genetic polymorphisms and risk of POAG through a case-control study in a Han population of China.METHODS: A total of 210 patients with POAG and 420 nor...AIM: To investigate the association between interleukin-10(IL-10) genetic polymorphisms and risk of POAG through a case-control study in a Han population of China.METHODS: A total of 210 patients with POAG and 420 normal subjects were recruited during the period from Dec. 2013 to Dec. 2016. The IL-10-1082 A>G(rs1800870),-819 T>C(rs1800871) and-592 C>A(rs1800872) polymorphisms were determined using iPlex GOLD SNP genotyping analysis(the SequenomMassARRAY? System, Sequenom, San Diego, USA). The association between IL-10-1082 A>G(rs1800870),-819 T>C(rs1800871), and-592 C>A(rs1800872) polymorphisms and risk of POAG was assessed by singlelogistic regression analysis.RESULTS: We observed that those carrying the CC genotype of rs1800871 was associated with an increased risk of POAG when compared with those harboring the TT genotype(OR=1.84, 95%CI=1.01-3.38). Those with AA genotype of rs1800872 had a 10.62 fold risk of POAG in comparison to the CC genotype(OR=10.62, 95%CI, 3.41-33.09). A completely linkage disequilibrium was found between IL-10 rs1800871-rs1800872(D’=1.00, r2=0.16). The A-C-A(OR=2.60, 95%CI, 1.48-4.58) and G-T-A(OR=2.34, 95%CI, 1.42-3.86) haplotypes were associated with an increased risk of POAG, while the A-T-C haplotype showed a decreased risk of POAG(OR=0.63, 95%CI, 0.49-0.81). CONCLUSION: Our data suggest that IL-10 rs1800871 and rs1800872 can be predictive factors for the pathogenesis of POAG in the Chinese population.展开更多
AIM:To demonstrate the possible associations between genetic polymorphisms of aldehyde dehydrogenase-2(ALDH2) and esophageal squamous cell dysplasia(ESCD).METHODS:All participants came from an area of high incidence o...AIM:To demonstrate the possible associations between genetic polymorphisms of aldehyde dehydrogenase-2(ALDH2) and esophageal squamous cell dysplasia(ESCD).METHODS:All participants came from an area of high incidence of esophageal cancer and underwent an endoscopic staining examination;biopsies were taken from a non-staining area of the mucosa and diagnosed by histopathology.Based on the examinations,the subjects were divided into the control group with normal esophageal squamous epithelial cells and the ESCD group.ALDH2 genotypes of 396 cases were determined including 184 ESCD cases and 212 controls.The odds ratio(OR) and 95% confidence intervals(95% CI) were calculated by binary logistic regression models.RESULTS:The distribution of ALDH2 genotypes showed significant differences between the two groups.The adjustment factors were gender and age in the logistic regression models.Compared with 2*2/2*2 genotype,2*1/2*1 genotype was found to be a risk factor for ESCD,and the OR(95% CI) was 4.50(2.21-9.19).There were significant correlations between ALDH2 genotypes and alcohol drinking/smoking/history of esophageal cancer.CONCLUSION:The ALDH2 polymorphism is significantly associated with ESCD.展开更多
基金supported by grants from the National Natural Science Foundation(Grant No.81972859 to WT)CAMS Innovation Fund for Medical Sciences(CIFMS)(Grant No.2019-I2M-1-003 to WT)the State Key Laboratory of Molecular Oncology Grant(Grant No.SKLMO-2021-03 to WT).
文摘Objective:The identification of biomarkers for predicting chemoradiotherapy efficacy is essential to optimize personalized treatment.This study determined the effects of genetic variations in genes involved in apoptosis,pyroptosis,and ferroptosis on the prognosis of patients with locally advanced rectal cancer receiving postoperative chemoradiotherapy(CRT).Methods:The Sequenom MassARRAY was used to detect 217 genetic variations in 40 genes from 300 patients with rectal cancer who received postoperative CRT.The associations between genetic variations and overall survival(OS)were evaluated using hazard ratios(HRs)and 95%confidence intervals(CIs)computed using a Cox proportional regression model.Functional experiments were performed to determine the functions of the arachidonate 5-lipoxygenase(ALOX5)gene and the ALOX5 rs702365 variant.Results:We detected 16 genetic polymorphisms in CASP3,CASP7,TRAILR2,GSDME,CASP4,HO-1,ALOX5,GPX4,and NRF2 that were significantly associated with OS in the additive model(P<0.05).There was a substantial cumulative effect of three genetic polymorphisms(CASP4 rs571407,ALOX5 rs2242332,and HO-1 rs17883419)on OS.Genetic variations in the CASP4 and ALOX5 gene haplotypes were associated with a higher OS.We demonstrated,for the first time,that rs702365[G]>[C]represses ALOX5 transcription and corollary experiments suggested that ALOX5 may promote colon cancer cell growth by mediating an inflammatory response.Conclusions:Polymorphisms in genes regulating cell death may play essential roles in the prognosis of patients with rectal cancer who are treated with postoperative CRT and may serve as potential genetic biomarkers for individualized treatment.
文摘Objective To investigate acid-suppression efficacy of proton pump inhibitors(PPIs) in relation to CYP2C19 genetic polymorphism on patients with peptic ulcer. Methods By an open, randomized and control trial, fifty nine patients with active peptic ulcer were randomly assigned to receive one of three PPIs on a single dose (20 mg of each drug): omeprazole group (n=19), rabeprazole group (n=20) and esomeprazole group (n=20). Intragastric pH was recorded 1 hour before and 24 hours after administration. CYP2C19 genotype was tested in all patients. Results The EMs/PMs ratio of each group was 16/3,17/3 and 17/3, respectively. The total time that intragastric pH>4, time percent pH>4 and median pH in PMs patients were significantly higher than those in EMs patients of omeprazole group (P<0.05). But all these differences were not found in rabeprazole group and esomeprazole group. The pH of nocturnal acid breakthrough(NAB) in both rabeprazole group and esomeprazole group was higher than that of omeprazole group, while there was no significant difference between rabeprazole group and esomeprazole group.Conclusion The acid-suppression efficacy of omeprazole is highly dependent on CYP2C19 genetic polymorphism, while CYP2C19 genetic polymorphism may have a little influence on the acid-suppression efficacy of rabeprazole and esomeprazole. The acid-suppression action of rabeprazole and esomeprazole is superior to omeprazole, especially on night acid secretion.
文摘Objective To analyze the genetic polymorphism of 6 STR loci (D12S358, D12S1675, D12S1663, D12S1697, D12S1725 and D12S1613) on chromosome 12 in Chinese Han population. Methods EDTA-blood specimens were collected from 153 unrelated individuals of Chinese Han population in Shaanxi province. Allele and genotype frequencies for the 6 STR loci were estimated and statistical parameters of polymorphism were calculated. Results 8 alleles and 18 genotypes, 10 alleles and 17 genotypes, 9 alleles and 15 genotypes, 12alleles and 29 genotypes, 12 alleles and 31 genotypes, 8 alleles and 11 genotypes were observed at D12S358, D12S1675, D12S1663, D12S1697, D12S1725 and D12S1613, respectively. No deviations of the observed allele frequency from Hardy-weinberg equilibrium expectations were found for any of these loci. The Heterozygotes of these 6 loci were 78.89%, 66.10%, 54.95%, 79.10%, 71.98% and 59.48%, respectively. It indicated the high genetic polymorphism of the loci in Chinese Han population. Conclusion The 6 STR loci belonged to the genetic marker system of high discriminutesation and high information in Chinese Han population and can be used in the study of gene-related diseases.
文摘Objective To reveal the relationship between the 5-HTTLPR and the Chinese Han nationality children with CA, compared the distribution of the 5-HTTLPR between the Han Chinese children with CA and healthy Han Chinese children ,and analyzed the association between the 5-HTTLPR and clinical symptoms of the Han Chinese children with CA. Methods Genomic DNAs of fifty subjects including 25 autistic children and 25 controls were extracted from blood samples. PCR amplification using Oligonucleotide primers flanking 5-HTTLPR was performed. Results ① Three kinds of alleles including the S (short) allele, the L (long) allele and the VL allele were found , and the 5-HTTLPR genotypes shown were S/S, L/L, S/L and L/VL. ② Allele frequencies did not differ significantly in patient groups in comparison with the control sample. No significant difference was identified between the observed 5-HTTLPR genotype distribution of the patient groups and control group. ③ The distribution of homozygous and heterozygous subjects between the two groups differed significantly. ④ The genotypes of the 5-HTTLPR polymorphism correlated significantly with the Body Movement Factor. ⑤ The allele frequency of healthy Han Chinese population and that of healthy Japanese population were similar. The frequency of S allele in not only autistic subjects but also healthy children in this study was considerably more than that in Caucasians and the frequency of L allele in our subjects decreased correspondingly. Conclusion ① A significant difference in the allele frequency between the Han Chinese and Caucasian populations was found. ② The genotypes of the 5-HTTLPR polymorphism correlated significantly with the Body Movement Factor of the patients. ③ The homozygote and the L allele were positively relevant to CA and they might be the risk factors of CA. The heterozygote and the S allele were negatively relevant to CA and they might be the protective factors of CA.
文摘While we studied pharmacokinetics of SM-12502 which was under development as an anti-PAF agent, we found three subjects showing a slow metabolic phenotype in its pharmacokinetics. Analyzing the genes for CYP2A6 from the three subjects, we discovered that the three subjects possessed the whole CYP2A6 gene deletion (CYP2A6*4C), a novel genetic polymorphism of the CYP2A6 gene. Genetically engineered Salmonella YG7108 cells expressing human CYP2A6 or CYP2E1 together with the NADPH-CYP reductase were established in our laboratory to compare the mutagen-producing capacity of these enzymes for various N-nitrosamines. We found that CYP2E1 was responsible for the metabolic activation of N-nitrosamines with relatively short alkyl chains, whereas CYP2A6 was involved in the metabolic activation of N-nitrosamines possessing relatively bulky alkyl chains such as a tobacco-specific nitrosamine, NNK, which has been known to cause lung tumor in rodents. Thus, to examine a hypothesis that individuals possessing the CYP2A6*4C have the reduced risk of lung cancer due to the lack of the capacity of the metabolic activation of certain carcinogens in tobacco smoke, a case-control study was performed.
文摘Objective To analyze the relationship between genetic polymorphisms of organic anion transporting polypeptide ( SLCO1B1 and SLCO1B3) and mycophenolic acid ( MPA) pharmacokinetics in Chinese kidney transplant recipients. Methods Gene mutations ( SLCO1B3 T334G,SLCO1B1 A338G) were detected in 68 recipi-
基金Supported by Natural Science Foundation of Fujian Province,China,No.C001009
文摘AIM: Genetic polymorphism in enzymes of carcinogen metabolism has been found to have the influence on the susceptibility to cancer. Cytochrome P450 2E1 ( CYP2 E1) is considered to play an important role in the metabolic activation of procarcinogens such as N-nitroscoamines and Iow molecular weight organic compounds. The purpose of this study is to determine whether CYP450 2Elpolymorphisms are associated with risk s of gastric cancer.METHODS: We conducted a population based case-control study in Changle county, Fujian Province, a high-risk region of gastric cancer in China. Ninety-one incident gastric cancer patients and ninety-four healthy controls were included in our study. Datas including dsmographic characteristcs, diet intake, and alcohol and tobacco consumption of indivduals in our study were completed by a standardized questionnaire. PCR-RFLP revealed three genotypes: heterozygote (C1/C2) and two homozygotes (C1/C1 and C2/C2) in CYP2E1.RESULTS: The frequency of variant genotypes (C1/C2 and C2/C2) in gastric cancer cases and controls was 36.3% and 24.5%, respectively. The rare homozygous C2/C2 genotype was found in 6 indivduals in gastric cancer group(6.6%),whereas there was only one in the control group (1.1%).However, there was no statistically significan difference between the two groups (two-tailed Fisher′s exact test, P =0.066). Indivduals in gastric cancer group were more likely to carry genotype C1/C2 (odds ratio, OR = 1.50) and C2/C2(OR = 7.34) than indivduals in control group (X2 = 4.597, for trend P=0.032). The frequencies of genofypes with the C2allele ( C1/C2 and C2/C2 genotypes) were compared with those of genotypes without C2 allele ( C1/C1 genotype )among indivduals in gastric cancer group and control group according to the pattern of gastric cancer risk factors. The results show that indivduals who exposed to these gastric cancer risk factors and carry the C2 allele seemed to have a higher risk of developing gastric cancer.CONCLUSION: Polymorphism of CYP2E1 gene may have some effct in the development of gastric cancer in Changle county, Fujian Province.
基金supported by a grant from the Youth Science Fund of Heilongjiang Province(No.QC08C77)
文摘BACKGROUND:Alcohol abuse and dependence are major factors in the pathogenesis of alcoholic liver disease(ALD).Alcohol abuse is becoming an increasingly severe problem among the Han,Mongol,and Korean nationalities in northeast China.This study aimed to investigate the relationship between ALD and the genetic polymorphism and expression levels of two enzymes,cytochrome P450ⅡE1(CYPⅡE1)and glutathione S-transferase P1(GSTP1)in patients of three nationalities.METHODS:Peripheral blood was collected from 353 Chinese patients with ALD,300 alcohol dependent patients without liver disease(alcoholic),and 360 healthy controls.Each group included patients from the Han,Mongol and Korean nationalities.Real-time polymerase chain reaction(PCR)and PCR-restriction fragment length polymorphism(PCR-RFLP)were used.RESULTS:Regardless of nationality,patients who carried the rare CYPⅡE1 C2 and GSTP1 Val alleles were at higher risk of ALD.The frequency of C2 and Val in patients with ALD was respectively 50.00% and 26.98% in the Han,31.36% and 22.87% in the Mongol,and 45.87% and 22.02% in the Korean nationality.No significant differences were seen in the frequency of either C2 or Val alleles in ALD patients among the three nationalities.In each nationality,the frequency of both C2 and Val alleles was significantly higher in ALD compared to alcoholic and healthy controls.Except for nationality,the average mRNA levels of CYPⅡ E1 in ALD patients and healthy controls were 10.05%and 2.21%,respectively.The average mRNA levels of GSTP1 in ALD patients and healthy controls were 0.53%and 2.12%,respectively.The mRNA level of CYPⅡE1 was higher,and that of GSTP1 was lower in patients with ALD compared to the controls.CONCLUSIONS:Except for nationality,patients with ALD in this series tended to have a higher mRNA expression of CYPⅡE1 and to carry the C2 allele,and tended to have a lower mRNA expression of GSTP1 and to carry the Val allele.There is a causal relationship between the polymorphic alleles,which leads to different mRNA levels and the development of ALD.
文摘Irritable bowel syndrome(IBS)is a complex symptombased disorder without established biomarkers or putative pathophysiology.IBS is a common functional gastrointestinal disorder which is defined as recurrent abdominal pain or discomfort that has at least two of the following symptoms for 3 d per month in the past 3mo according to ROMEⅢ:relief by defecation,onset associated with a change in stool frequency or onset with change in appearance or form of stool.Recent discoveries revealed genetic polymorphisms in specific cytokines and neuropeptides may possibly influence the frequencies and severity of symptoms,as well as the therapeutic responses in treating IBS patients.This review gives new insights on how genetic determinations influence in clinical manifestations,treatment responses and potential biomarkers of IBS.
基金the Science and Technology Development Fund,Ministry of Scientific Research Egypt,Project No.1587Cairo University
文摘AIM: To correlate a genetic polymorphism of the low-density lipoprotein(LDL) receptor with antiviral responses in Egyptian chronic hepatitis C virus(HCV) patients.METHODS: Our study included 657 HCV-infected patients with genotype 4 who received interferonbased combination therapy. Patients were divided into two groups based on their response to therapy: 356 were responders, and 301 were non-responders. Patients were compared to 160 healthy controls. All patients and controls underwent a thorough physical examination, measurement of body mass index(BMI) and the following laboratory tests: serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, albumin, total bilirubin, direct bilirubin, prothrombin time, prothrombin concentration, INR, complete blood count, serum creatinine, fasting blood sugar, HCV antibody, and hepatitis B surface antigen. All HCV patients were further subjected to the following laboratory tests: HCV-RNA using quantitative polymerase chain reaction(PCR), antinuclear antibodies, thyroid-stimulating hormone, an LDL receptor(LDLR) genotype study of LDLR exon8 c.1171G>A and exon-10 c.1413G>A using real-time PCR-based assays, abdominal ultrasonography, ultrasonographic-guided liver biopsy, and histopathological examination of liver biopsies. Correlations of LDL receptor polymorphisms with HAI, METAVIR score, presence of steatosis, and BMI were performed in all cases.RESULTS: There were no statistically significant differences in response rates between the different types of interferon used or LDLR exon10 c.1413G>A. However, there was a significant difference in the frequency of the LDL receptor exon8 c.1171G>A genotype between cases(AA: 25.9%, GA: 22.2%, GG: 51.9%) and controls(AA: 3.8%, GA: 53.1% and GG: 43.1%)(P < 0.001). There was a statistically significant difference in the frequency of the LDLR exon 8C:1171 G>A polymorphism between responders(AA: 3.6%, GA: 15.2%, GG: 81.2%) and nonresponders(AA: 52.2%, GA: 30.6%, GG: 17.2%)(P < 0.001). The G allele of LDL receptor exon8 c.1171G>A predominated in cases and controls over the A allele, and a statistically significant association with response to interferon was observed. The frequency of the LDLR exon8 c.1171G>A allele in non-responders was: A: 67.4% and G: 32.6 vs A: 11.2% and G: 88.8% in responders(P < 0.001). Therefore, carriers of the A allele exhibited a 16.4 times greater risk for nonresponse. There was a significant association between LDL receptors exon8 c.1171G>A and HAI(P < 0.011). There was a significant association between LDL receptors exon8 c.1171G>A and BMI. The mean BMI level was highest in patients carrying the AA genotype(28.7 ± 4.7 kg/m2) followed by the GA genotype(28.1 ± 4.8 kg/m2). The lowest BMI was the GG genotype(26.6 ± 4.3 kg/m2)(P < 0.001). The only significant associations were found between LDL receptors exon8 c.1171G>A and METAVIR score or steatosis(P < 0.001).CONCLUSION: LDL receptor gene polymorphisms play a role in the treatment response of HCV and the modulation of disease progression in Egyptiansinfected with chronic HCV.
基金Supported by the Program of International S&T Cooperation,No.2014DFA31850National Natural Science Foundation of China,No.81870379.
文摘Genetic polymorphism is associated with irritable bowel syndrome(IBS)in terms of susceptibility and clinical manifestations.Previous studies have shown that genetic polymorphism might play a key role in the onset and progression of IBS by modulating components of its pathogenesis such as the gut-brain axis,gastrointestinal motility,inflammatory activity,and immune status.Although underlying pathophysiological mechanisms have not been fully clarified,the potential ethnic differences that are present in worldwide genetic studies of IBS deserve attention.This review surveyed numerous studies focusing on IBSassociated single nucleotide polymorphisms,and investigated the ethnic disparities revealed by them.The results demonstrate the need for more attention on ethnic factors in IBS-related genetic studies.Taking ethnic backgrounds into accounts and placing emphasis on disparities potentially ascribed to ethnicity could help lay a solid and generalized foundation for transcultural,multi-ethnic,or secondary analyses in IBS,for example,a meta-analysis.Broader genetic studies considering ethnic factors are greatly needed to obtain a better understanding of the pathophysiological mechanisms of IBS and to improve the prevention,intervention,and treatment of this disease.
文摘AIM:To investigate the correlation between interleukin-18(IL-18) gene polymorphisms and the risk of developing Crohn's disease(CD).METHODS:The PubMed,CISCOM,CINAHL,Web of Science,EBSCO,Cochrane Library,MEDLINE,EMBASE and CBM databases were searched without any language restrictions using combinations of keywords relating to CD and IL-18 for relevant articles published before November 1st,2013.Screening of the published studies retrieved from searches was based on our stringent inclusion and exclusion criteria and resulted in seven eligible studies for meta-analysis.A metaanalysis was conducted using a random-effects model with STATA 12.0 software.Crude odds ratios(ORs) with95%confidence intervals(95%CI) were calculated.RESULTS:Seven case-control studies,with a total of1930 CD cases and 1930 healthy subjects,met our inclusion criteria.The results of our meta-analysis indicated that the IL-18 rs1946518 A>C and rs187238G>C polymorphisms may correlate with an increased risk of CD under five genetic models(all P < 0.05).Furthermore,we observed positive associations between the IL-18 rs360718 A>C polymorphism and CD risk under three genetic models(C allele vs A allele:OR = 2.03,95%CI:1.20-3.43,P = 0.008;CC vs AA+AC:OR = 2.39,95%CI:1.2-4.43,P = 0.006;CC vs AC:OR = 2.31,95%CI:1.22-4.38,P = 0.010).However,such associations were not found for the IL-18 rs917997 C>T,codon 35 A>C and rs1946519G>T polymorphisms(all P> 0.05).A subgroup analysis was conducted to investigate the effect of ethnicity on an individual's susceptibility to CD.Our results revealed positive correlations between IL-18 genetic polymorphisms and an increased risk of CD among Asians and Africans(all P < 0.05),but not among Caucasians(all P> 0.05).CONCLUSION:This meta-analysis indicated that the IL-18 rs1946518 A> C,rs187238 G>C and rs360718A>C polymorphisms may contribute to susceptibility to CD,especially among Asians and Africans.These polymorphisms are known to reduce IL-18 mRNA and protein levels.
文摘interleukin(iL)28B genetic polymorphism is significantly associated with the sustained virological response rate in patients with chronic hepatitis C treated with pegylated interferon-α(PEG-iFN)plus ribavirin and with spontaneous hepatitis C virus clearance.However,a consensus on the relationship between iL28B genetic polymorphism and the favorable outcome of chronic hepatitis B virus infection defined by hepatitis B e antigen seroconversion,and/or hepatitis B surface antigen seroclearance in patients treated with interferon or PEG-iFN has not been reached.Several reports failed to show a positive association,while some studies demonstrated a positive association in certain subject settings.More prospective studies including large cohorts are needed to determine the possible association between iL28B genetic polymorphism and the outcome of interferon or PEG-iFN treatment for chronic hepatitis B.
基金supported by "Strategic Scholarships Fellowships Fromtier Research Network"from the Commission Higher Education(Thailand) (Grant No.CHE-PhD-SW-INV-20060169)also parially supported by the China Medical Board,Faculty of Public Health,Mahidol University,Bangkok,Thailand
文摘Objective:To investigate the genetic polymorphism of Plasmodium vivax(P.vivax) PvCSP and PvMSP1 genes from field isolates at four endemic regions(North,East,West and South) of Thailand.Methods:The 152 P.vivax injected cases from dried blood spots were DMA extracted and confirmed by species-specific primer sets using multiplex PCR method.PvMSPI fragments F2 and F3:PvCSP were gcnotvped using RFLP-PCR method.Resuits:Totally amplified DNA which was multiple genotypes for PvMSP1 F2 and PvMSP1 F3 were 12.50%and 8.55%.respectively while PvCSP was 3.95%.The overall frequency of multiple genotypes was 25%.There were 12 allele tvpes of PvMSP1 F2 using AluI enzyme digestion and 8 size variations were found in P\MSP1 F3.The isolates from western region was highly genetic diverse when compare among all isolates.The predominant variant type of PvCSP gene was \ K2I0 type.Conclusions:The niulliple genotypes are common found in Thailand and it might hide the real genotype.PvCSP does not have extensive genetic diversity in this study.However.PvMSPI marker due to multiple genotypes is difficult In be analyzed.The multiple genotypes findings might stem from population migration and vector species findings.
基金supported by grants from the National Natural Science Foundation of China (81101840)the National Natural Science Foundation of Innovation Group of China(81121002)the National S&T Major Project of China(2012ZX10002017)
文摘BACKGROUND:Recurrence of hepatocellular carcinoma(HCC) after liver transplantation(LT) remains one of the most common causes of poor long-term survival.However,the host genetic factors affecting increased risk of tumor recurrence after transplantation have not been thoroughly elucidated.The present study was designed to investigate the association of cytokine gene polymorphisms with the risk of tumor recurrence in LT patients for HCC.METHODS:Eleven single-nucleotide polymorphisms within the promoter regions of 7 cytokine genes,i.e.,the IL-1 family(IL-1α and IL-1β),IL-6,IL-8,IL-10,TNF-α,and TGF-β1,were genotyped in 93 HCC patients treated with LT using DNA sequencing.The association between these polymorphisms and the risk of tumor recurrence was evaluated while controlling confounding clinical variables.RESULTS:The genotype frequency of IL-10-1082 A/G in patients with and without recurrence of HCC was AA 83.3%,GA 16.7% and AA 97.6%,GA 2.4%,respectively.The association between IL-10-1082 GA and recurrence was significant(P=0.033).No other single-nucleotide polymorphism in the cytokine gene was found to be associated with recurrence.Kaplan-Meier survival curves showed that the homozygous AA patients had a significantly longer mean recurrence-free survival than heterozygous GA patients(23.5 vs 5.7 months,P=0.001).However,multivariate analysis failed to reveal that the GA genotype of IL-10-1082 A/G was an independent indicator of recurrence.CONCLUSIONS:This study suggests the lack of association of selected cytokine gene polymorphisms with HCC recurrence after LT in the Han Chinese population.The finding does not exclude the idea that other cytokine polymorphisms could act as candidate biomarkers of disease prognosis.
基金Supported by Agencies viz Department of Biotechnology(DBT),Indian Council of Medical Research(ICMR),Department of Science and Technology(DST)and Centre of Excellence(COE),UP Government,India for generous grants to our laboratory for diabetes research
文摘Diabetes mellitus is a combined metabolic disorder which includes hyperglycemia,dyslipidemia,stroke and several other complications.Various groups all over the world are relentlessly working out the possible role of a vast number of genes associated with type 2 diabetes(T2DM).Inflammation is an important outcome of any kind of imbalance in the body and is therefore an indicator of several diseases,including T2DM.Various ethnic populations around the world show different levels of variations in single nucleotide polymorphisms(SNPs).The present review was undertaken to explore the association of cytokine gene polymorphisms with T2DM in populations of different ethnicities.This will lead to the understanding of the role of cytokine genes in T2DM risk and development.Association studies of genotypes of SNPs present in cytokine genes will help to identify risk haplotype(s)for disease susceptibility by developing prognostic markers and alter treatment strategies for T2DM and related complications.This will enable individuals at risk to take prior precautionary measures and avoid or delay the onset of the disease.Future challenges will be to understand the genotypic interactions between SNPs in one cytokine gene or several genes at different loci and study their association with T2DM.
文摘Objective: In the past few decades, more than 500 reports have been published on the relationship between single nucleotide polymorphisms(SNPs) on candidate genes and gastric cancer(GC) risk. Previous findings have been disputed and are controversial. Therefore, we performed this article to summarize and assess the credibility and strength of genetic polymorphisms on the risk of GC.Methods: We used Web of Science, PubMed, and Medline to identify meta-analyses published before July 30 th, 2018 that assessed associations between variants on candidate genes and the risk of GC. Cumulative epidemiological evidence of statistical associations was assessed combining Venice criteria and a false-positive report probability(FPRP) test.Results: Sixty-one variants demonstrated a significant association with GC risk, whereas 29 demonstrated no association. Nine variants on nine genes were rated as presenting strong cumulative epidemiological evidence for a nominally significant association with GC risk, including APE1(rs1760944), DNMT1(rs16999593), ERCC5(rs751402), GSTT1(null/presence), MDM2(rs2278744), PPARG(rs1801282), TLR4(rs4986790), IL-17 F(rs763780), and CASP8(rs3834129). Eleven SNPs were rated as moderate, and 33 SNPs were rated as weak. We also used the FPRP test to identify 13 noteworthy SNPs in five genome-wide association studies.Conclusions: Sixty-one variants are significantly associated with GC risk, and 29 variants are not associated with GC risk;however, five variants on five genes presented strong evidence for an association upgraded from moderate. Further study of these variants may be needed in the future. Our study also provides referenced information for the genetic predisposition to GC.
基金supported by the National Natural Science Foundation of China,No.81070913(to ZYH)
文摘Two common polymorphisms of the peroxisome proliferator-activated receptor gamma(PPARG) gene, rs1801282 and rs3856806, may be important candidate gene loci affecting the susceptibility to ischemic stroke. This case-control study sought to identify the relationship between these two single-nucleotide polymorphisms and ischemic stroke risk in a northern Chinese Han population. A total of 910 ischemic stroke participants were recruited from the First Hospital of China Medical University, Shenyang, China as a case group, of whom 895 completed the study. The 883 healthy controls were recruited from the Health Check Center of the First Hospital of China Medical University, Shenyang, China. All participants or family members provided informed consent. The study protocol was approved by the Ethics Committee of the First Hospital of China Medical University, China on February 20, 2012(approval No. 2012-38-1). The protocol was registered with the Chinese Clinical Trial Registry(registration number: ChiCTR-COC-17013559). Plasma genomic DNA was extracted from all participants and analyzed for rs1801282 and rs3856806 single nucleotide polymorphisms using a SNaPshot Multiplex sequencing assay. Odds ratios(ORs) and 95% confidence intervals(CIs) were calculated using unconditional logistic regression to estimate the association between ischemic stroke and a particular genotype. Results demonstrated that the G allele frequency of the PPARG gene rs1801282 locus was significantly higher in the case group than in the control group(P < 0.001). Individuals carrying the G allele had a 1.844 fold increased risk of ischemic stroke(OR = 1.844, 95% CI: 1.286–2.645, P < 0.001). Individuals carrying the rs3856806 T allele had a 1.366 fold increased risk of ischemic stroke(OR = 1.366, 95% CI: 1.077–1.733, P = 0.010). The distribution frequencies of the PPARG gene haplotypes rs1801282-rs3856806 in the control and case groups were determined. The frequency of distribution in the G-T haplotype case group was significantly higher than that in the control group. The risk of ischemic stroke increased to 2.953 times in individuals carrying the G-T haplotype(OR = 2.953, 95% CI: 2.082–4.190, P < 0.001). The rs1801282 G allele and rs3856806 T allele had a multiplicative interaction(OR = 3.404, 95% CI: 1.631–7.102, P < 0.001) and additive interaction(RERI = 41.705, 95% CI: 14.586–68.824, AP = 0.860;95% CI: 0.779–0.940;S = 8.170, 95% CI: 3.772–17.697) on ischemic stroke risk, showing a synergistic effect. Of all ischemic stroke cases, 86% were attributed to the interaction of the G allele of rs1801282 and the T allele of rs3856806. The effect of the PPARG rs1801282 G allele on ischemic stroke risk was enhanced in the presence of the rs3856806 T allele(OR = 8.001 vs. 1.844). The effect of the rs3856806 T allele on ischemic stroke risk was also enhanced in the presence of the rs1801282 G allele(OR = 2.546 vs. 1.366). Our results confirmed that the G allele of the PPARG gene rs1801282 locus and the T allele of the rs3856806 locus may be independent risk factors for ischemic stroke in the Han population of northern China, with a synergistic effect between the two alleles.
文摘AIM: To investigate the association between interleukin-10(IL-10) genetic polymorphisms and risk of POAG through a case-control study in a Han population of China.METHODS: A total of 210 patients with POAG and 420 normal subjects were recruited during the period from Dec. 2013 to Dec. 2016. The IL-10-1082 A>G(rs1800870),-819 T>C(rs1800871) and-592 C>A(rs1800872) polymorphisms were determined using iPlex GOLD SNP genotyping analysis(the SequenomMassARRAY? System, Sequenom, San Diego, USA). The association between IL-10-1082 A>G(rs1800870),-819 T>C(rs1800871), and-592 C>A(rs1800872) polymorphisms and risk of POAG was assessed by singlelogistic regression analysis.RESULTS: We observed that those carrying the CC genotype of rs1800871 was associated with an increased risk of POAG when compared with those harboring the TT genotype(OR=1.84, 95%CI=1.01-3.38). Those with AA genotype of rs1800872 had a 10.62 fold risk of POAG in comparison to the CC genotype(OR=10.62, 95%CI, 3.41-33.09). A completely linkage disequilibrium was found between IL-10 rs1800871-rs1800872(D’=1.00, r2=0.16). The A-C-A(OR=2.60, 95%CI, 1.48-4.58) and G-T-A(OR=2.34, 95%CI, 1.42-3.86) haplotypes were associated with an increased risk of POAG, while the A-T-C haplotype showed a decreased risk of POAG(OR=0.63, 95%CI, 0.49-0.81). CONCLUSION: Our data suggest that IL-10 rs1800871 and rs1800872 can be predictive factors for the pathogenesis of POAG in the Chinese population.
基金Supported by The Project of National Natural Science Foundation of China,No.30571601the 2004 Key Special Project of Scientific and Technological Development in Shandong Province,China,No.2004GG1108039the 2007 Special Foundation for Postdoctoral Innovation Subject in Shandong Province of China,No.200702034
文摘AIM:To demonstrate the possible associations between genetic polymorphisms of aldehyde dehydrogenase-2(ALDH2) and esophageal squamous cell dysplasia(ESCD).METHODS:All participants came from an area of high incidence of esophageal cancer and underwent an endoscopic staining examination;biopsies were taken from a non-staining area of the mucosa and diagnosed by histopathology.Based on the examinations,the subjects were divided into the control group with normal esophageal squamous epithelial cells and the ESCD group.ALDH2 genotypes of 396 cases were determined including 184 ESCD cases and 212 controls.The odds ratio(OR) and 95% confidence intervals(95% CI) were calculated by binary logistic regression models.RESULTS:The distribution of ALDH2 genotypes showed significant differences between the two groups.The adjustment factors were gender and age in the logistic regression models.Compared with 2*2/2*2 genotype,2*1/2*1 genotype was found to be a risk factor for ESCD,and the OR(95% CI) was 4.50(2.21-9.19).There were significant correlations between ALDH2 genotypes and alcohol drinking/smoking/history of esophageal cancer.CONCLUSION:The ALDH2 polymorphism is significantly associated with ESCD.
